The long range goal of this research program is to elucidate the regulatory role of nucleic acids in the cell body and axoplasm of neurons. Cytoplasmic nucleic acids may be involved in the modulation of the neuronal periphery (ie. axons and synaptic terminals). Recently we have demonstrated that axoplasmic RNA from squid and Myxicola giant axons is primarily low molecular weight. Experiments are planned to determine whether this RNA is functional transfer RNA and to evaluate the possibility that an enzyme exists in the axon and synapse which employs transfer RNA to add amino acids to the NH2- terminal position of axonal and synaptic proteins. Evidence indicates that axoplasmic RNA is synthesized at the level of the axon. The location of the DNA template for axoplasmic RNA synthesis will be defined. The mitochondrion represents an essential organelle in axonal and synaptic function. However, practically nothing is known about the neuronal mechanisms which provide for the replacement of mitochondria which turnover in the axon and synaptic terminal. I propose to use mitochondrial DNA as a specific mitochondrial marker to study the replication and migration of mitochondria in the axon. This study will have the added goal of determining whether a non-mitochondrial cytoplasmic DNA exists in the axoplasm. In another part of this program Dr. Ruth Nordlander and I will carry out a morphological analysis of the development of a specific form of interaction between embryonic and regenerating neurons. The fusion of neurons in polycheates and molluscs which results in the production of enormous syncytial giant axons will be studied by light and electron microscopy.